We plan to study in detail the responses to various labeled digitalis glycosides in intact anesthetized dogs after varying periods of digitalis infusion in such a way as to maintain constant pre-determined plasma levels. The responses will include cardiac mechanical responses (left ventricle dP/Qt, right ventricle contractile force) and electrical responses, tissue uptake of digitalis, and membrane Na-K-ATPase activity. By determining the time course of the development of these responses to digitaloids of different physical properties, it is hoped that it will be possible to determine whether Na-K-ATPase inhibition is responsible for the positive inotropic or for the toxic effects of digitalis administration.